This Week in Pediatric Oncology
2014-02
Episodes
Monday Feb 10, 2014
Monday Feb 10, 2014
August
01, 2013
In this new episode, host Dr. Tim Cripe
(Nationwide Children's) and co-host Dr. Jeffrey Auletta (Nationwide Children's)
interview Solving Kids' Cancer co-founder and Executive Director Scott Kennedy
and co-director of research programs Donna Ludwinski. Both Scott and Donna
share their personal stories that led them to Solving Kids' Cancer and their
shared passion to improve survival for children with the deadliest childhood
cancers through research advocacy.
Monday Feb 10, 2014
Monday Feb 10, 2014
May
07, 2012
In this interesting episode, host Dr. Tim Cripe
(Nationwide Children's) and co-hosts Dr. Lionel Chow (Cincinnati Children's),
Dr. Andy Kolb (AI DuPont), and Donna Ludwinski (Solving Kids' Cancer) quiz Dr
Paul Sondel and Dr. Ken DeSantes (both from University of Wisconsin - Madison)
on NK cells and the implications of KIR/KIR-ligand mismatch (killer
immunoglobulin-like receptor) with regard to immunotherapy treatment of
neuroblastoma.
References:
Delgado DC, Hank JA, Kolesar J, Lorentzen D, et
al. Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the
response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res.
2010 Dec 1;70(23):9554-61. Epub 2010 Oct 8.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999644/
.
Venstrom JM, Zheng J, Noor N, Danis KE, et al.
KIR and HLA genotypes are associated with disease progression and survival
following autologous hematopoietic stem cell transplantation for high-risk
neuroblastoma. Clin Cancer Res. 2009 Dec 1;15(23):7330-4. Epub 2009 Nov 24.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788079/
.
Alderson KL, Sondel PM. Clinical cancer therapy
by NK cells via antibody-dependent cell-mediated cytotoxicity. J Biomed
Biotechnol. 2011;2011:379123. Epub 2011 May 24.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110303/
Monday Feb 10, 2014
Monday Feb 10, 2014
April
05, 2012
Host Dr. Tim Cripe welcomes back co-host Dr.
Lionel Chow to discuss somatic mutations in pediatric brain tumors. After
recapping the consensus paper on molecular subgroups in medulloblastoma
discussed in TWiPO episode 22 (Brain Tumor Round Robin) Dr Chow highlights the
significance of the driver mutations in histone H3.3 in pediatric glioblastoma.
Results of whole exome sequencing have shown that significantly more somatic
mutations are present in adult tumors compared to pediatric tumors. This
difference might suggest a reason for better success rates in pediatric tumors
and possibly more escape mechanisms in adult tumors. Dr. Chow also discusses a
paper published by the Pediatric Cancer Genome Project (a St. Jude Children's
Research Hospital–Washington University collaboration) on somatic histone H3
alterations in diffuse intrinsic pontine glioma (DIPG). The findings are
significant in showing that this mutation is present in 36% of non-brain stem
gliomas and in 78% of brain stem gliomas, but in none of the other pediatric
tumor types.
Please send comments and questions to
twipo@solvingkidscancer.org
Papers discussed:
Taylor MD, Northcott PA, Korshunov A, et al.
Molecular subgroups of medulloblastoma: the current consensus. Acta
Neuropathol. 2012 Apr;123(4):465-72. Epub 2011 Dec 2.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306779/
Schwartzentruber J, Korshunov A, Liu XY, Jones
DT, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in
paediatric glioblastoma. Nature. 2012 Jan 29;482(7384):226-31. doi:
10.1038/nature10833. http://www.ncbi.nlm.nih.gov/pubmed/22286061
Wu G, Broniscer A, McEachron TA, Lu C, Paugh
BS, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic
pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012 Jan
29;44(3):251-3. doi: 10.1038/ng.1102. St. Jude Children's Research
Hospital–Washington University Pediatric Cancer Genome Project.http://www.ncbi.nlm.nih.gov/pubmed/22286216
Monday Feb 10, 2014
Monday Feb 10, 2014
March
06, 2012
Dr. Tim Cripe welcomes Dr. Andy Kolb from AI
DuPont in this episode of TWiPO, and special guest Dr. Andromachi Scaradavou,
the Medical Director of New York Blood Center's National Cord Blood Program.
NYBC is the world's oldest and largest public
cord blood bank, and collects, processes, tests and stores cord blood that
mothers donate shortly after birth. The cord blood is for children and adults
with no related donor available who need a hematopoietic stem cell transplant
for life-threatening illnesses. More than 60,000 units are stored at NYBC and
more than 4500 units have been provided for transplants worldwide. The variety
of ethic groups represented is much higher in cord blood banking than in bone
marrow donor programs. The percentage of use is climbing significantly for
pediatric transplants partly because of the small dose required.
Discussants cover many aspects of this
fascinating subject: background and uses of cord blood, logistics of
collecting, processing, storing, and selecting units for transplants, as well
as the advantages and challenges currently faced in this field. For more on
NYBC seehttp://www.nationalcordbloodprogram.org/
We welcome all questions or comments at
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
January
26, 2012In 2011 there were over 1300 new articles
published on neuroblastoma in the medical literature.
Join Dr. Tim Cripe and his co-host Dr. Lars
Wagner in a fast-paced, in-depth, and comprehensive survey of 18 of the most
important papers on neuroblastoma published in 2011. Dr. Cripe and Dr Wagner
explore and discuss the compelling evidence reported on a variety of topics,
including epidemiology, risk stratification, clinical trials, ALK mutation and
expression, new targets, and genetics.
All of the papers discussed are listed HERE with links to PubMed.
Please send all comments and questions to twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
December
05, 2011
Join Dr. Tim Cripe and his co-host Dr. Lionel
Chow for a fast-paced, in-depth, and comprehensive survey of 15 important
recent papers on pediatric brain tumor research, addressing medulloblastoma,
ependymomas, and gliomas. Dr. Cripe and Dr. Chow explore and discuss the
compelling evidence reported on a variety of topics, including viral causes and
therapeutic implications, biomarkers, genomics, proteomics, targets, classification,
risk stratification, treatment side-effects, proton-beam radiation therapy, and
results of recent clinical trials.
This robust review of current research includes
all of the following papers [click link], listed by timed location in the podcast.
Please send all comments and questions to
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
November
29, 2011
Dr. Tim Cripe and co-hosts Dr. Maureen O'Brien
and Dr. Raj Nagarajan interview a pediatric hematology/oncology legend, Dr.
Beatrice Lampkin, who served as Director of Cincinnati Children's Division of
Hematology/Oncology in the 1970’s. This enlightening and inspiring discussion
explores her career and her contributions to leukemia therapy and the
challenges she faced as an early leader in the field as a female. She describes
her experience with polio, paralysis from the neck down, crutches for mobility,
and later, her confinement to a wheelchair. Revealing another era in
communications with parents and patients in the 1960s and 1970s, she explains
how parents were advised to use the term "anemia" to describe their
child's condition rather than "leukemia" to to explain why the child
would require periodic blood transfusions, in order to prevent shunning by
friends and family. Dr. Lampkin also shares her satisfaction in following the
earliest survivors of pediatric cancer she treated who are now in their 40s and
50s.
As if all that isn't inspiring enough, she
describes her busy retirement in which she continues to teach the Cincinnati
Children's Hospital fellows how to examine blood and bone marrow smears under
the microscope and her work in the founding of the GLAD House (http://www.gladhouse.org/),
a sanctuary to help drug-addicted youth get off the streets.
Please send all comments and questions to
twipo@solvingkidscancer.org.
Monday Feb 10, 2014
Monday Feb 10, 2014
November
15, 2011
Today’s episode features an impressive lineup
for a hot topic. Host Dr. Tim Cripe warns: “If your blood isn’t boiling by the
end, you weren't listening.” Hear Tim and co-host Dr. Lionel Chow discuss
pediatric cancer research funding with guests Dr. C. Patrick (Pat) Reynolds, Dr.
E. Anders (Andy) Kolb, and parent Joe McDonough.
Dr. Pat Reynolds puts government spending on
the number one disease killer of children in the US in perspective, comparing
the tiny $200M spent on pediatric cancer research to the foreign aid budget of
$22B (less than 1%). For example, $1.6B goes to Egypt alone. The COG budget is
a mere $46M. The DOD budget is $700B. See his slides here. Dr. Lionel Chow mentions an enlightening fact
– private donations to St Jude exceed $600M per year, on top of the givers’
paying taxes. This is 3 times the entire NCI budget for pediatric cancer
research for all institutions in the US.
Spending per Person Years Life Lost is compared
for childhood cancers and adult cancers, see graph here.
Dr. C Patrick Reynolds is Director, Cancer
Center and Professor of Cell Biology & Biochemistry, Internal Medicine, and
Pediatrics, School of Medicine, Texas Tech University Health Sciences Center,
Lubbock TX. Dr. E Anders Kolb is the Director of Blood and Bone Marrow
Transplantation at Alfred I. duPont Hospital for Children, and Head of the
Cancer Therapeutics Laboratory at Nemours Biomedical Research, Wilmington, DE.
Joe McDonough is father to Andrew, and founder of The Andrew McDonough B+ (Be Positive)
Foundation, raising money for families and research.
Please send comments to
twipo@solvingkidscancer.org
Monday Feb 10, 2014
Monday Feb 10, 2014
October
30, 2011Several just-published papers in the literature
relate to recent podcast episodes, and host Dr. Tim Cripe and co-host Dr. Lionel Chow review these interesting
developments.
0:55 Hedgehog Signaling: Recent papers
discussing this pathway in neuroblastoma and rhabdomyosarcoma are discussed,
with implications for treatment in these tumor types with itraconozole.
6:40 Cell phone and brain tumor risk: The
controversy concerning criticism by the Environmental Health Trust of a study
showing that cell phone use does not increase risk of brain tumors in children
is explored.
Accelerated approval of cancer drugs by the FDA
and implications for pediatric cancers.
15:30 Brentuximab for two types of lymphoma
21:20 Vemurafenib for melanoma
28:30 Crizotinib for non-small cell lung cancer
(and potential use in neuroblastoma)
42:30 Response to email regarding personalized
medicine TWiPO episode #17 and lab blog for Dr Charles Keller at OHSU
References:
Pediatr Blood Cancer. 2011 Dec 1;57(6):930-8.
doi: 10.1002/pbc.23174. Hedgehog pathway activity in
pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: a report
from the Children's Oncology Group.
Int J Oncol. 2011 Oct;39(4):899-906. doi:
10.3892/ijo.2011.1076. Pharmacological inhibition of
the Hedgehog pathway preventshuman rhabdomyosarcoma cell growth.
Cancer Lett. 2011 Nov 28;310(2):222-31. Inhibition of the sonic hedgehog
pathway by cyplopaminereduces the CD133+/CD15+ cell compartment and the in
vitrotumorigenic capability of neuroblastoma cells.
Cell Phone Study Was Flawed, Say Some Experts by
Roxanne Nelson Medscape Oncology News.
The JNCI Study by Aydin et al on Risk of Childhood Brain Cancer from
Cellphone Use Reveals Serious Health Problems, Environmental Health Trust.
N Engl J Med. 2010 Nov 4;363(19):1812-21. Brentuximab
vedotin (SGN-35) for relapsed CD30-positive lymphomas.
FDA Approves Brentuximab for Two Lymphomas By:
ELIZABETH MECHCATIE, Oncology Report Digital Network.
Clin Cancer Res. 2011 Oct
15;17(20):6428-36. Brentuximab Vedotin (SGN-35).
FDA Approves Vemurafenib for Advanced Melanoma.
By: JANE SALODOF MACNEIL, Oncology Report Digital Network.
N Engl J Med. 2011 Jun
30;364(26):2507-16. Improved survival with
vemurafenib in melanoma with BRAFV600E mutation.
N Engl J Med. 2011 Jun 30;364(26):2547-8. Been
there, not done that--melanoma in the age of molecular therapy. http://www.ncbi.nlm.nih.gov/pubmed/21639809
Biochem J. 2011 Aug 15. Activating ALK mutations found in neuroblastoma are inhibited by
Crizotinib and NVP-TAE684.
N Engl J Med. 2010 Oct
28;363(18):1693-703. Anaplastic lymphoma kinase inhibition in non-small-cell
lung cancer.
Nature. 2007 Aug 2;448(7153):561-6. Epub 2007
Jul 11. Identification of the transforming EML4-ALK fusion gene in non-small-cell
lung cancer.
Science. 1994 Mar 4;263(5151):1281-4. Fusion of a kinase gene, ALK, to
a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
Monday Feb 10, 2014
Monday Feb 10, 2014
October
18, 2011
Host Dr. Tim Cripe and co-host Dr. Lionel Chow
welcome special guest Dr. Jeff Toretsky on TWiPO to discuss his clinical and
research interest in Ewing's sarcoma. Dr. Toretsky explains the challenges of
developing a clinical grade drug from a small molecule for a specific target
such as EWS-FLI1. The small market for a disease like Ewing's creates
formidable hurdles for researchers, yet Dr. Toretsky is driven on by the
question "If I don't do this, who will?" (17:54 mins)
Dr. Jeff Toretsky is Professor of Oncology and
Pediatrics at Georgetown University. He graduated with BS in Biochemistry from
University of Wisconsin, Madison, WI, and recieved his MD from University of
Minnesota, Minneapolis, MN. He completed fellowship training at the NCI
Pediatric Branch.
Please send any questions or comments to
twipo@solvingkidscancer.org